Of radioactive transition metals used in radio-pharmaceuticals, .sup.99m Tc is a nuclide most often used in the field of radiopharmaceuticals for diagnostic imaging, and .sup.186 Re and .sup.188 Re are nuclides preferably used in the field of radiopharmaceuticals for therapy. Since these radioactive transition metals have different coordination numbers in different oxidized states and can form various complexes together with various ligands, they are used usually in the form of a complex. For example, as a process for producing the complex, there is a process of chelating ligands with Tc atom at first, and then attaching a physiologically active substance to the chelate, or a process of attaching a physiologically active substance to ligands at first, and then coordinating a Tc atom therewith. Whichever process is employed, it is usually difficult to carry out the above-mentioned attachment while maintaining the whole activity of the physiologically active substance. Such attachment is more difficult particularly in the case of a small compound.
There has recently been proposed a process comprising replacing a part of a physiologically active substance by a complex containing a metal ion, without impairing the activity of the substance (D. Y. Chi et al., J. Med. Chem. 1994, 37, 928-937). This process is advantageous in that a metal-containing block is accurately attached to the physiologically active substance, so that a structure very close to that of the original physiologically active substance can be maintained. However, no generally applicable process has yet been established.
Transition metal nitride complexes are excellent in stability to hydrolysis. Therefore, when a transition metal nitride complex is subjected to exchange reaction with any of various ligands having a useful physiological activity, when used in a pharmaceutical, the nitride group of the nitride complex can remain bonded strongly to the metal atom. Accordingly, transition metal nitride complexes having various substituents have been proposed. For example, WO 90/06137 discloses diethyl bisdithiocarbamate-Tc nitride complex, dimethyl bisdithiocarbamate-Tc nitride complex, di-n-propyl bisdithiocarbamate-Tc nitride complex, N-ethyl-N-(2-ethoxyethyl)bisdithiocarbamate-Tc nitride complex, etc.
In addition, WO 89/08657 discloses a process for producing a transition metal nitride complex which comprises reacting a phosphine-based ligand like a polyphosphine as a reducing agent for the transition metal with the transition metal oxide, then reacting a nitride of a metal or ammonium as a nitrogen source for nitride with the reaction product to convert it to the corresponding nitride, and then coordinating a physiologically active monoclonal antibody or the like with this nitride.
In these processes, the choice of the ligand having a physiological active group is so important that it determines properties of the resulting pharmaceutical. But, the metal nitride complex can have various numbers of coordination positions from mono-dentate to quadridentate and hence is formed in plural forms. Therefore, it has been difficult to obtain a single complex stoichiometrically having a specific physiologically active ligand.